Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast formation in vitro

Balga, Renate; Wetterwald, Antoinette; Portenier, Jeannette; Dolder, Silvia; Mueller, Christoph; Hofstetter, Willy (2006). Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast formation in vitro. Bone, 39(2), pp. 325-35. New York, N.Y.: Elsevier 10.1016/j.bone.2006.02.056

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TNFalpha is known to stimulate the development and activity of osteoclasts and of bone resorption. The cytokine was found to mediate bone loss in conjunction with inflammatory diseases such as rheumatoid arthritis or chronic aseptic inflammation induced by wear particles from implants and was suggested to be a prerequisite for the loss of bone mass under estrogen deficiency. In the present study, the regulation of osteoclastogenesis by TNFalpha was investigated in co-cultures of osteoblasts and bone marrow or spleen cells and in cultures of bone marrow and spleen cells grown with CSF-1 and RANKL. Low concentrations of TNFalpha (1 ng/ml) caused a >90% decrease in the number of osteoclasts in co-cultures, but did not affect the development of osteoclasts from bone marrow cells. In cultures with p55TNFR(-/-) osteoblasts and wt BMC, the inhibitory effect was abrogated and TNFalpha induced an increase in the number of osteoclasts in a dose-dependent manner. Osteoblasts were found to release the inhibitory factor(s) into the culture supernatant after simultaneous treatment with 1,25(OH)(2)D(3) and TNFalpha, this activity, but not its release, being resistant to treatment with anti-TNFalpha antibodies. Dexamethasone blocked the secretion of the TNFalpha-dependent inhibitor by osteoblasts, while stimulating the development of osteoclasts. The data suggest that the effects of TNFalpha on the differentiation of osteoclast lineage cells and on bone metabolism may be more complex than hitherto assumed and that these effects may play a role in vivo during therapies for inflammatory diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Wetterwald, Antoinette; Müller, Christoph and Hofstetter, Willy

ISSN:

8756-3282

ISBN:

16580896

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:48

Last Modified:

17 Mar 2015 21:48

Publisher DOI:

10.1016/j.bone.2006.02.056

PubMed ID:

16580896

Web of Science ID:

000238708400013

URI:

https://boris.unibe.ch/id/eprint/19911 (FactScience: 2988)

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